NM_002424.3:c.102+72G>A

Variant names:

• chr11-102724682-C-T
• rs11225394
• NM_002424.3:c.102+72G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002424.3(MMP8):​c.102+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,314,524 control chromosomes in the GnomAD database, including 42,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (3069 hom., cov: 33)
  • Exomes 𝑓: 0.25 (38961 hom.)
• Consequence: MMP8 NM_002424.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 25 publications found

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	NM_002424.3	MANE Select	c.102+72G>A		intron	N/A	NP_002415.1
	MMP8	NM_001304441.2		c.-59+72G>A		intron	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.-56+72G>A		intron	N/A	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.102+72G>A		intron	N/A	ENSP00000236826.3
	MMP8	ENST00000438475.2	TSL:5	c.27+72G>A		intron	N/A	ENSP00000401004.2
	MMP8	ENST00000528662.6	TSL:5	n.102+72G>A		intron	N/A	ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27180 AN: 152030 Hom.: 3066 Cov.: 33

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.252 AC: 293140 AN: 1162374 Hom.: 38961 AF XY: 0.250 AC XY: 143827 AN XY: 576010

African (AFR) AF: 0.0369 AC: 940 AN: 25492

American (AMR) AF: 0.216 AC: 6288 AN: 29062

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 3428 AN: 19100

East Asian (EAS) AF: 0.0764 AC: 2638 AN: 34550

South Asian (SAS) AF: 0.164 AC: 9557 AN: 58228

European-Finnish (FIN) AF: 0.259 AC: 11857 AN: 45754

Middle Eastern (MID) AF: 0.131 AC: 614 AN: 4700

European-Non Finnish (NFE) AF: 0.275 AC: 246950 AN: 897914

Other (OTH) AF: 0.228 AC: 10868 AN: 47574

GnomAD4 genome AF: 0.179 AC: 27182 AN: 152150 Hom.: 3069 Cov.: 33 AF XY: 0.177 AC XY: 13179 AN XY: 74364

African (AFR) AF: 0.0472 AC: 1961 AN: 41536

American (AMR) AF: 0.198 AC: 3027 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5180

South Asian (SAS) AF: 0.150 AC: 725 AN: 4824

European-Finnish (FIN) AF: 0.235 AC: 2481 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17265 AN: 67976

Other (OTH) AF: 0.171 AC: 360 AN: 2110

Alfa AF: 0.232 Hom.: 2334

Bravo AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.23
PhyloP100		-1.2
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11225394; hg19: chr11-102595413;